Shift in emergency department utilization by frequent attendees with sickle cell disease during the COVID-19 pandemic: A multicentre cohort study.

While the coronavirus disease-2019 (COVID-19) might have increased acute episodes in people living with sickle cell disease (SCD), it may also have changed their reliance on emergency department (ED) services. We assessed the impact of the COVID-19 pandemic and lockdowns on ED visits in adult SCD people followed in five French reference centres, with a special focus on 'high users' (≥10 visits in 2019). We analysed the rate of ED visits from 1 January 2015 to 31 December 2021, using a self-controlled case series. Among 1530 people (17 829 ED visits), we observed a significant reduction in ED visits during and after lockdowns, but the effect vanished over time. Compared to pre-pandemic, incidence rate ratios for ED visits were 0.59 [95% CI 0.52-0.67] for the first lockdown, 0.66 [95% CI 0.58-0.75] for the second and 0.85 [95% CI 0.73-0.99] for the third. High users (4% of people but 33.7% of visits) mainly drove the reductions after the first lockdown. COVID-19 lockdowns were associated with reduced ED visits. While most people returned to their baseline utilization by April 2021, high users had a lasting decrease in ED visits. Understanding the factors driving the drop in ED utilization among high users might inform clinical practice and health policy.

Finite Width of Anyons Changes Their Braiding Signature.

Anyons are particles intermediate between fermions and bosons, characterized by a nontrivial exchange phase, yielding remarkable braiding statistics. Recent experiments have shown that anyonic braiding has observable consequences on edge transport in the fractional quantum Hall effect (FQHE). Here, we study transport signatures of anyonic braiding when the anyons have a finite width. We show that the width of the anyons, even when extremely small, can have a tremendous impact on transport properties and braiding signatures. In particular, we find that taking the finite width into account allows us to explain recent experimental results on the FQHE at filling factor 2/5 [M. Ruelle et al., Phys. Rev. X 13, 011031 (2023)PRXHAE2160-330810.1103/PhysRevX.13.011031]. Our work shows that the finite width of anyons crucially influences setups involving anyonic braiding, especially when the exchange phase is larger than π/2.

Levitons in correlated nano-scale systems.

In this short review (written to celebrate David Campbell's 80th birthday), we provide a theoretical description of quantum transport in nanoscale systems in the presence of single-electron excitations generated by Lorentzian voltage drives, termed Levitons. These excitations allow us to realize the analog of quantum optics experiments using electrons instead of photons. Importantly, electrons in condensed matter systems are strongly affected by the presence of different types of non-trivial correlations, with no counterpart in the domain of photonic quantum optics. After providing a short introduction about Levitons in non-interacting systems, we focus on how they operate in the presence of two types of strong electronic correlations in nanoscale systems, such as those arising in the fractional quantum Hall effect or in superconducting systems. Specifically, we consider Levitons in a quantum Hall bar of the fractional quantum Hall effect, pinched by a quantum point contact, where anyons with fractional charge and statistics tunnel between opposite edges. In this case, a Leviton-Leviton interaction can be induced by the strongly correlated background. Concerning the effect of superconducting correlations on Levitons, we show that, in a normal metal system coupled to BCS superconductors, half-integer Levitons minimize the excess noise in the Andreev regime. Interestingly, energy-entangled electron states can be realized on-demand in this type of hybrid setup by exploiting crossed Andreev reflection. The results exposed in this review have potential applications in the context of quantum information and computation with single-electron flying qubits.

Anyonic Statistics Revealed by the Hong-Ou-Mandel Dip for Fractional Excitations.

The fractional quantum Hall effect (FQHE) is known to host anyons, quasiparticles whose statistics is intermediate between bosonic and fermionic. We show here that Hong-Ou-Mandel (HOM) interferences between excitations created by narrow voltage pulses on the edge states of a FQHE system at low temperature show a direct signature of anyonic statistics. The width of the HOM dip is universally fixed by the thermal time scale, independently of the intrinsic width of the excited fractional wave packets. This universal width can be related to the anyonic braiding of the incoming excitations with thermal fluctuations created at the quantum point contact. We show that this effect could be realistically observed with periodic trains of narrow voltage pulses using current experimental techniques.

Bone microstructure and volumetric bone mineral density in patients with hyperuricemia with and without psoriasis.

We analyzed volumetric bone mineral density (vBMD) and bone microstructure using HR-pQCT in subjects with normouricemia (NU) and subjects with hyperuricemia (HU) with and without psoriasis (PSO). HU was associated with higher cortical vBMD and thickness. Differences in average and trabecular vBMD were found between patients with PSO + HU and NU. INTRODUCTION: Hyperuricemia (HU) and gout are co-conditions of psoriasis and psoriatic arthritis. Current data suggest a positive association between HU and areal bone mineral density (BMD) and a negative influence of psoriasis on local bone, even in the absence of arthritis. However, the influence of the combination of HU and psoriasis on bone is still unclear. The aim of this study was to assess the impact of HU with and without psoriasis on bone microstructure and volumetric BMD (vBMD). METHODS: Healthy individuals with uric acid levels within the normal range (NU), with hyperuricemia (HU), patients with hyperuricemia and psoriasis (PSO + HU), and patients with uric acid within the normal range and psoriasis (PSO + NU) were included in our study. Psoriasis patients had no current or past symptoms of arthritis. Average, trabecular, and cortical vBMD (mgHA/cm3); trabecular number (Tb.N, 1/mm) and thickness (Tb.Th, mm); inhomogeneity of the network (1/N.SD, mm); and cortical thickness (Ct.Th., mm) were carried out at the ultradistal radius using high-resolution peripheral quantitative computed tomography. In addition, bone turnover markers such as DKK-1, sclerostin, and P1NP were analyzed. RESULTS: In total, 130 individuals were included (44 NU participants (34% female), 50 HU (24%), 16 PSO + HU (6%), 20 PSO + NU (60%)). Subjects were aged: NU 54.5 (42.8, 62.1), HU 57.5 (18.6, 65.1), PSO + HU 52.0 (42.3, 57.8), and PSO + NU 42.5 (34.8, 56.8), respectively. After adjusting for age, sex, BMI, and diabetes, patients in the HU group revealed significantly higher values of cortical vBMD (p < 0.001) as well as cortical thickness (p = 0.04) compared to the NU group. PSO + NU showed no differences to NU, but PSO + HU demonstrated both lower average (p = 0.03) and trabecular vBMD (p = 0.02). P1NP was associated with average, cortical, and trabecular vBMD as well as cortical thickness while sclerostin levels were related to trabecular vBMD. CONCLUSION: Hyperuricemia in otherwise healthy subjects was associated with a better cortical vBMD and higher cortical thickness. However, patients with both psoriasis and hyperuricemia revealed a lower vBMD.

Negative Delta-T Noise in the Fractional Quantum Hall Effect.

We study the current correlations of fractional quantum Hall edges at the output of a quantum point contact subjected to a temperature gradient. This out-of-equilibrium situation gives rise to a form of temperature-activated shot noise, dubbed delta-T noise. We show that the tunneling of Laughlin quasiparticles leads to a negative delta-T noise, in stark contrast with electron tunneling. Moreover, varying the transmission of the quantum point contact or applying a voltage bias across the Hall bar may flip the sign of this noise contribution, yielding signatures that can be accessed experimentally.

The ageing joint-standard age- and sex-related values of bone erosions and osteophytes in the hand joints of healthy individuals.

OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.

Giant Shot Noise from Majorana Zero Modes in Topological Trijunctions.

The clear-cut experimental identification of Majorana bound states in transport measurements still poses experimental challenges. We here show that the zero-energy Majorana state formed at a junction of three topological superconductor wires is directly responsible for giant shot noise amplitudes, in particular at low voltages and for small contact transparency. The only intrinsic noise limitation comes from the current-induced dephasing rate due to multiple Andreev reflection processes.

Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes.

OBJECTIVE: Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. METHODS: We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. RESULTS: We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p c = 2.34E- 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p c = 2.40E- 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. CONCLUSION: Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.

Estimation of π-π Electronic Couplings from Current Measurements.

The π-π interactions between organic molecules are among the most important parameters for optimizing the transport and optical properties of organic transistors, light-emitting diodes, and (bio-) molecular devices. Despite substantial theoretical progress, direct experimental measurement of the π-π electronic coupling energy parameter t has remained an old challenge due to molecular structural variability and the large number of parameters that affect the charge transport. Here, we propose a study of π-π interactions from electrochemical and current measurements on a large array of ferrocene-thiolated gold nanocrystals. We confirm the theoretical prediction that t can be assessed from a statistical analysis of current histograms. The extracted value of t ≈35 meV is in the expected range based on our density functional theory analysis. Furthermore, the t distribution is not necessarily Gaussian and could be used as an ultrasensitive technique to assess intermolecular distance fluctuation at the subangström level. The present work establishes a direct bridge between quantum chemistry, electrochemistry, organic electronics, and mesoscopic physics, all of which were used to discuss results and perspectives in a quantitative manner.

Minimal Excitations in the Fractional Quantum Hall Regime.

We study the minimal excitations of fractional quantum Hall edges, extending the notion of levitons to interacting systems. Using both perturbative and exact calculations, we show that they arise in response to a Lorentzian potential with quantized flux. They carry an integer charge, thus involving several Laughlin quasiparticles, and leave a Poissonian signature in a Hanbury Brown-Twiss partition noise measurement at low transparency. This makes them readily accessible experimentally, ultimately offering the opportunity to study real-time transport of Abelian and non-Abelian excitations.

Surfing on Protein Waves: Proteophoresis as a Mechanism for Bacterial Genome Partitioning.

Efficient bacterial chromosome segregation typically requires the coordinated action of a three-component machinery, fueled by adenosine triphosphate, called the partition complex. We present a phenomenological model accounting for the dynamic activity of this system that is also relevant for the physics of catalytic particles in active environments. The model is obtained by coupling simple linear reaction-diffusion equations with a proteophoresis, or "volumetric" chemophoresis, force field that arises from protein-protein interactions and provides a physically viable mechanism for complex translocation. This minimal description captures most known experimental observations: dynamic oscillations of complex components, complex separation, and subsequent symmetrical positioning. The predictions of our model are in phenomenological agreement with and provide substantial insight into recent experiments. From a nonlinear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and traveling wave regimes triggered by the dynamical spontaneous breaking of rotational symmetry.

Sialylation of anti-histone immunoglobulin G autoantibodies determines their capabilities to participate in the clearance of late apoptotic cells.

The Fc portion of immunoglobulin (Ig)G harbours a single glycosylation site. Glycan sialylation is critical for structure and for certain effector functions of IgG. Anti-histone IgG of patients with systemic lupus erythematosus is reportedly responsible for the recruitment of polymorphonuclear cells (PMN) to the clearance of apoptotic cells. Autoantibodies decorating secondary necrotic cells (SNEC) induce proinflammatory responses after activation of blood-borne phagocytes. Analysing the sialylation status of affinity-purified anti-histone IgG in patients with systemic lupus erythematosus (SLE), we demonstrated that the anti-histone IgG was contained preferentially in the non-sialylated fraction. In functional ex-vivo phagocytosis studies, non-sialylated anti-SNEC IgG directed SNEC preferentially into PMN but did not change their cytokine secretion profiles. In contrast, sialylated IgG reduced the phagocytosis by monocytes of SNEC. Moreover, the sialylated anti-SNEC IgG was not simply anti-inflammatory, but switched the cytokine secretion profiles from interleukin (IL)-6/IL-8 to tumour necrosis factor (TNF)-α/IL-1ß. Here we describe how different sialylation statuses of IgG autoantibodies contribute to the complex inflammatory network that regulates chronic inflammation.

[Do we still need clinical studies in rheumatology?]. / Brauchen wir noch klinische Studien in der Rheumatologie?

Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.

[High-resolution peripheral quantitative CT (HR-pQCT). New insights into arthritis]. / Hochauflösende periphere quantitative CT (HR-pQCT). Neue Einblicke in die Arthritis.

The detection of periarticular bone lesions is of crucial importance in the diagnosis and treatment monitoring of chronic inflammatory diseases such as, but not limited to, rheumatoid arthritis (RA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was initially developed for the meticulous assessment of bone microstructure with a focus on bone density parameters. With an isotropic voxel size of 82 µm HR-pQCT is, however, also well suited for quantitative evaluation of periarticular bone lesions, such as erosion, osteophytes as well as bone surface changes in arthritis. The present article gives an overview of the manifold possibilities of application of this novel imaging modality and addresses potential benefits of this technique for rheumatology in the future.

Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation.

Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing-remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood.

Scattering theory of non-equilibrium noise and deltaTcurrent fluctuations through a quantum dot.

We consider the non-equilibrium zero frequency noise generated by a temperature gradient applied on a device composed of two normal leads separated by a quantum dot. We recall the derivation of the scattering theory for non-equilibrium noise for a general situation where both a bias voltage and a temperature gradient can coexist and put it in a historical perspective. We provide a microscopic derivation of zero frequency noise through a quantum dot based on a tight binding Hamiltonian, which constitutes a generalization of the seminal result obtained for the current in the context of the Keldysh formalism. For a single level quantum dot, the obtained transmission coefficient entering the scattering formula for the non-equilibrium noise corresponds to a Breit-Wigner resonance. We compute the delta-Tnoise as a function of the dot level position, and for a broad range of values of the dot level width, in the Breit-Wigner case, for two relevant situations which were considered recently in two separate experiments. In the regime where the two reservoir temperatures are comparable, our gradient expansion shows that the delta-Tnoise is dominated by its quadratic contribution, and is minimal close to resonance. In the opposite regime where one reservoir is much colder, the gradient expansion fails and we find the noise to be typically linear in temperature before saturating. In both situations, we conclude with a short discussion of the case where both a voltage bias and a temperature gradient are present, in order to address the potential competition with thermoelectric effects.

[Large-joint synovectomy in the era of biological therapies]. / Synovektomie der großen Gelenke in der Ära der Biologika.

Since the mid 1980s, a global decrease in surgical procedures related to rheumatoid arthritis (RA) has been documented for joint-preserving procedures such as synovectomy as well as joint replacement surgery. This reflects improvements in the early management of rheumatoid arthritis and availability of more effective medical treatment. The present review summarizes the recent literature on the frequency of orthopaedic surgery in RA patients as well as the role of synovectomy in the rheumatoid hip, knee and shoulder in times of biological RA therapy.